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class=\u0022elements-frag-data highwire-markup\u0022 id=\u0022fig-data\u0022\u003E\u003Cdiv id=\u0022fig-data-figures\u0022 class=\u0022group frag-figure\u0022\u003E\u003Cdiv class=\u0022fig-data-title-jump clearfix\u0022\u003E\u003Ch3 class=\u0022fig-data-group-title\u0022\u003EFigures\u003C\/h3\u003E\u003Cdiv class=\u0022fig-data-jump-links\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022item-list\u0022\u003E\u003Cul class=\u0022fig-data-list clearfix\u0022 id=\u0022fragments-fig\u0022\u003E\u003Cli class=\u0022first\u0022\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion \u0022 id=\u0022F1\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The induction of LTP by activation of the postsynaptic cAMP pathway paired with \u0026#x3B8; frequency synaptic stimulation. A, Postsynaptic blockade of the cAMP pathway prevents TPS-LTP. A1, The graph shows the time course of the mean intracellular EPSP slope; thearrow denotes the time of TPS. In cells exposed to 1 \u0026#x3BC;m isoproterenol in the superfusate (horizontal bar), TPS induced a slowly developing LTP (filled circles; n = 6). When TPS was delivered in the absence of isoproterenol (open circles; n = 6), a nonsignificant trend toward synaptic depression was observed (ANOVA, p\u0026gt; 0.10). Intracellular injection of Rp-cAMPS (filled triangles; n = 5) blocked LTP after a transient potentiation. All groups differed from one another over the last 5 min of recording (final 3 time points; Newman\u0026#x2013;Keuls test, allp values \u0026lt; 0.05).A2 , Sample traces, withtop and bottom panels showing intracellular and corresponding field potentials, respectively, are presented. Traces were obtained during the baseline period and at 30 min after TPS (arrow). Calibration: 20 mV intracellular, 500 \u0026#x3BC;V extracellular; 5 msec. Note that the inhibition of LTP by Rp-cAMPS was restricted to the recorded cell.B, Summary of intracellular and field results from all slices is shown. The data were obtained 30 min after TPS.C, The pairing of TPS with 8-Br-cAMP induces LTP. 8-Br-cAMP (500 \u0026#x3BC;m) was applied in the superfusate for 30 min (indicated by the gray horizonal arrow), ending with the delivery of TPS (black arrow). LTP was induced only when TPS was paired with 8-Br-cAMP. Inset, Representativetraces are shown. Calibration: 200 \u0026#x3BC;V; 5 msec.D, 8-Br-cAMP does not regulate NMDA receptor-mediated EPSPs (n = 5). Field recordings were obtained in low Mg2+ (nominally 50 \u0026#x3BC;m) and in the presence of 10 \u0026#x3BC;m DNQX. EPSPs were recorded during a train of TPS before 8-Br-cAMP application and after 8-Br-cAMP washout (combined as control, filled bar) and in the presence of 500 \u0026#x3BC;m 8-Br-cAMP (hatched bar). The data indicate the mean slope of the final 10 stimuli in the train. There were no statistically significant group differences (paired t test, p \u0026gt; 0.10).ISO, Isoproterenol.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-990087893\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;The induction of LTP by activation of the postsynaptic cAMP pathway paired with \u0026#x3B8; frequency synaptic stimulation. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;, Postsynaptic blockade of the cAMP pathway prevents TPS-LTP. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;\u0026lt;sub\u0026gt;\u0026lt;em\u0026gt;1\u0026lt;\/em\u0026gt;\u0026lt;\/sub\u0026gt;, The graph shows the time course of the mean intracellular EPSP slope; the\u0026lt;em\u0026gt;arrow\u0026lt;\/em\u0026gt; denotes the time of TPS. In cells exposed to 1 \u0026#x3BC;m isoproterenol in the superfusate (\u0026lt;em\u0026gt;horizontal bar\u0026lt;\/em\u0026gt;), TPS induced a slowly developing LTP (\u0026lt;em\u0026gt;filled circles\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 6). When TPS was delivered in the absence of isoproterenol (\u0026lt;em\u0026gt;open circles\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 6), a nonsignificant trend toward synaptic depression was observed (ANOVA, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt;\u0026gt; 0.10). Intracellular injection of Rp-cAMPS (\u0026lt;em\u0026gt;filled triangles\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5) blocked LTP after a transient potentiation. All groups differed from one another over the last 5 min of recording (final 3 time points; Newman\u0026#x2013;Keuls test, all\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; values \u0026lt; 0.05).\u0026lt;em\u0026gt;A\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt; \u0026lt;\/em\u0026gt;, Sample \u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt;, with\u0026lt;em\u0026gt;top\u0026lt;\/em\u0026gt; and \u0026lt;em\u0026gt;bottom panels\u0026lt;\/em\u0026gt; showing intracellular and corresponding field potentials, respectively, are presented. \u0026lt;em\u0026gt;Traces\u0026lt;\/em\u0026gt; were obtained during the baseline period and at 30 min after TPS (\u0026lt;em\u0026gt;arrow\u0026lt;\/em\u0026gt;). Calibration: 20 mV intracellular, 500 \u0026#x3BC;V extracellular; 5 msec. Note that the inhibition of LTP by Rp-cAMPS was restricted to the recorded cell.\u0026lt;em\u0026gt;B\u0026lt;\/em\u0026gt;, Summary of intracellular and field results from all slices is shown. The data were obtained 30 min after TPS.\u0026lt;em\u0026gt;C\u0026lt;\/em\u0026gt;, The pairing of TPS with 8-Br-cAMP induces LTP. 8-Br-cAMP (500 \u0026#x3BC;m) was applied in the superfusate for 30 min (indicated by the \u0026lt;em\u0026gt;gray horizonal arrow\u0026lt;\/em\u0026gt;), ending with the delivery of TPS (\u0026lt;em\u0026gt;black arrow\u0026lt;\/em\u0026gt;). LTP was induced only when TPS was paired with 8-Br-cAMP. \u0026lt;em\u0026gt;Inset\u0026lt;\/em\u0026gt;, Representative\u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt; are shown. Calibration: 200 \u0026#x3BC;V; 5 msec.\u0026lt;em\u0026gt;D\u0026lt;\/em\u0026gt;, 8-Br-cAMP does not regulate NMDA receptor-mediated EPSPs (\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5). Field recordings were obtained in low Mg\u0026lt;sup\u0026gt;2+\u0026lt;\/sup\u0026gt; (nominally 50 \u0026#x3BC;m) and in the presence of 10 \u0026#x3BC;m DNQX. EPSPs were recorded during a train of TPS before 8-Br-cAMP application and after 8-Br-cAMP washout (combined as control, \u0026lt;em\u0026gt;filled bar\u0026lt;\/em\u0026gt;) and in the presence of 500 \u0026#x3BC;m 8-Br-cAMP (\u0026lt;em\u0026gt;hatched bar\u0026lt;\/em\u0026gt;). The data indicate the mean slope of the final 10 stimuli in the train. There were no statistically significant group differences (paired \u0026lt;em\u0026gt;t\u0026lt;\/em\u0026gt; test, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026gt; 0.10).\u0026lt;em\u0026gt;ISO\u0026lt;\/em\u0026gt;, Isoproterenol.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 1.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F1.medium.gif\u0022 width=\u0022440\u0022 height=\u0022417\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 1.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F1.medium.gif\u0022 width=\u0022440\u0022 height=\u0022417\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/421046\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 1.\u003C\/span\u003E \u003Cp id=\u0022p-12\u0022\u003EThe induction of LTP by activation of the postsynaptic cAMP pathway paired with \u03b8 frequency synaptic stimulation. \u003Cem\u003EA\u003C\/em\u003E, Postsynaptic blockade of the cAMP pathway prevents TPS-LTP. \u003Cem\u003EA\u003C\/em\u003E\u003Csub\u003E\u003Cem\u003E1\u003C\/em\u003E\u003C\/sub\u003E, The graph shows the time course of the mean intracellular EPSP slope; the\u003Cem\u003Earrow\u003C\/em\u003E denotes the time of TPS. In cells exposed to 1 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E isoproterenol in the superfusate (\u003Cem\u003Ehorizontal bar\u003C\/em\u003E), TPS induced a slowly developing LTP (\u003Cem\u003Efilled circles\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 6). When TPS was delivered in the absence of isoproterenol (\u003Cem\u003Eopen circles\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 6), a nonsignificant trend toward synaptic depression was observed (ANOVA, \u003Cem\u003Ep\u003C\/em\u003E\u0026gt; 0.10). Intracellular injection of Rp-cAMPS (\u003Cem\u003Efilled triangles\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 5) blocked LTP after a transient potentiation. All groups differed from one another over the last 5 min of recording (final 3 time points; Newman\u2013Keuls test, all\u003Cem\u003Ep\u003C\/em\u003E values \u0026lt; 0.05).\u003Cem\u003EA\u003Csub\u003E2\u003C\/sub\u003E\n\u003C\/em\u003E, Sample \u003Cem\u003Etraces\u003C\/em\u003E, with\u003Cem\u003Etop\u003C\/em\u003E and \u003Cem\u003Ebottom panels\u003C\/em\u003E showing intracellular and corresponding field potentials, respectively, are presented. \u003Cem\u003ETraces\u003C\/em\u003E were obtained during the baseline period and at 30 min after TPS (\u003Cem\u003Earrow\u003C\/em\u003E). Calibration: 20 mV intracellular, 500 \u03bcV extracellular; 5 msec. Note that the inhibition of LTP by Rp-cAMPS was restricted to the recorded cell.\u003Cem\u003EB\u003C\/em\u003E, Summary of intracellular and field results from all slices is shown. The data were obtained 30 min after TPS.\u003Cem\u003EC\u003C\/em\u003E, The pairing of TPS with 8-Br-cAMP induces LTP. 8-Br-cAMP (500 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) was applied in the superfusate for 30 min (indicated by the \u003Cem\u003Egray horizonal arrow\u003C\/em\u003E), ending with the delivery of TPS (\u003Cem\u003Eblack arrow\u003C\/em\u003E). LTP was induced only when TPS was paired with 8-Br-cAMP. \u003Cem\u003EInset\u003C\/em\u003E, Representative\u003Cem\u003Etraces\u003C\/em\u003E are shown. Calibration: 200 \u03bcV; 5 msec.\u003Cem\u003ED\u003C\/em\u003E, 8-Br-cAMP does not regulate NMDA receptor-mediated EPSPs (\u003Cem\u003En\u003C\/em\u003E = 5). Field recordings were obtained in low Mg\u003Csup\u003E2+\u003C\/sup\u003E (nominally 50 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) and in the presence of 10 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E DNQX. EPSPs were recorded during a train of TPS before 8-Br-cAMP application and after 8-Br-cAMP washout (combined as control, \u003Cem\u003Efilled bar\u003C\/em\u003E) and in the presence of 500 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E 8-Br-cAMP (\u003Cem\u003Ehatched bar\u003C\/em\u003E). The data indicate the mean slope of the final 10 stimuli in the train. There were no statistically significant group differences (paired \u003Cem\u003Et\u003C\/em\u003E test, \u003Cem\u003Ep\u003C\/em\u003E \u0026gt; 0.10).\u003Cem\u003EISO\u003C\/em\u003E, Isoproterenol.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion \u0022 id=\u0022F2\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022TPS evokes complex potentials when paired with isoproterenol. A, Representative fieldtraces recorded immediately before the start of TPS (PRE) and at every 30th stimulus during TPS. In the absence of isoproterenol (top records), no spikes were seen during TPS. The increase in the duration of the EPSP relative to the baseline was typically observed in this experiment. When isoproterenol was present (bottom traces), the unitary EPSP was replaced by a complex waveform, which included spike potentials. Calibration: 500 \u0026#x3BC;V; 10 msec. B, Summary of the number of discrete components in sampled fieldtraces during TPS in the absence (hatched bars; n = 5) and presence (filled bars; n = 5) of 1 \u0026#x3BC;m isoproterenol. The groups differed significantly (p \u0026lt; 0.02), and there was no patterning effect during TPS (F \u0026lt; 1).\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-990087893\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;TPS evokes complex potentials when paired with isoproterenol. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;, Representative field\u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt; recorded immediately before the start of TPS (\u0026lt;em\u0026gt;PRE\u0026lt;\/em\u0026gt;) and at every 30th stimulus during TPS. In the absence of isoproterenol (\u0026lt;em\u0026gt;top records\u0026lt;\/em\u0026gt;), no spikes were seen during TPS. The increase in the duration of the EPSP relative to the baseline was typically observed in this experiment. When isoproterenol was present (\u0026lt;em\u0026gt;bottom traces\u0026lt;\/em\u0026gt;), the unitary EPSP was replaced by a complex waveform, which included spike potentials. Calibration: 500 \u0026#x3BC;V; 10 msec. \u0026lt;em\u0026gt;B\u0026lt;\/em\u0026gt;, Summary of the number of discrete components in sampled field\u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt; during TPS in the absence (\u0026lt;em\u0026gt;hatched bars\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5) and presence (\u0026lt;em\u0026gt;filled bars\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5) of 1 \u0026#x3BC;m isoproterenol. The groups differed significantly (\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.02), and there was no patterning effect during TPS (\u0026lt;em\u0026gt;F\u0026lt;\/em\u0026gt; \u0026lt; 1).\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 2.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F2.medium.gif\u0022 width=\u0022368\u0022 height=\u0022440\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 2.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F2.medium.gif\u0022 width=\u0022368\u0022 height=\u0022440\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/421048\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 2.\u003C\/span\u003E \u003Cp id=\u0022p-17\u0022\u003ETPS evokes complex potentials when paired with isoproterenol. \u003Cem\u003EA\u003C\/em\u003E, Representative field\u003Cem\u003Etraces\u003C\/em\u003E recorded immediately before the start of TPS (\u003Cem\u003EPRE\u003C\/em\u003E) and at every 30th stimulus during TPS. In the absence of isoproterenol (\u003Cem\u003Etop records\u003C\/em\u003E), no spikes were seen during TPS. The increase in the duration of the EPSP relative to the baseline was typically observed in this experiment. When isoproterenol was present (\u003Cem\u003Ebottom traces\u003C\/em\u003E), the unitary EPSP was replaced by a complex waveform, which included spike potentials. Calibration: 500 \u03bcV; 10 msec. \u003Cem\u003EB\u003C\/em\u003E, Summary of the number of discrete components in sampled field\u003Cem\u003Etraces\u003C\/em\u003E during TPS in the absence (\u003Cem\u003Ehatched bars\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 5) and presence (\u003Cem\u003Efilled bars\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 5) of 1 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E isoproterenol. The groups differed significantly (\u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.02), and there was no patterning effect during TPS (\u003Cem\u003EF\u003C\/em\u003E \u0026lt; 1).\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion \u0022 id=\u0022F3\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The role of protein phosphatase-1 in TPS-induced LTP. A, Protein phosphatase activity in CA1 is inhibited by activation of the cAMP pathway. In slices exposed to 1 mm 8-Br-cAMP for 30 min, total phosphatase activity was significantly lower than that in untreated controls (p \u0026lt; 0.05). Similar results were obtained in two independent experiments. The selectivity of the assay for PP1 is shown by the ability of 100 nm thiophosphorylated inhibitor-1 (I-1-P) to block \u0026gt;85% of total phosphatase activity, indicated by the black bar and dashed line. B, Endogenous protein phosphatase inhibitor-1 is phosphorylated by stimulation of the cAMP pathway. Tissue homogenates were probed with a monoclonal antibody recognizing either the phosphorylated form of inhibitor-1 selectively (top gel) or both the phosphorylated and nonphosphorylated inhibitor-1 (bottom gel). Isoproterenol (10 \u0026#x3BC;m) and 8-Br-cAMP (500 \u0026#x3BC;m) increased the levels of Thr35-phosphorylated I-1 4.04 (\u0026#xB1; 2.28)-fold and 2.75 (\u0026#xB1; 0.62)-fold, respectively, relative to unstimulated tissue and normalized for total I-1 levels. Both isoproterenol and 8-Br-cAMP increased the level of thiophosphorylated inhibitor-1 (top gel) without significantly changing the total amount of inhibitor-1. Similar results were obtained in two other experiments.C, Postsynaptic inhibition of PP1 mimics cAMP pathway activation in TPS-LTP. C1, The time course of LTP induced by TPS paired with thiophosphorylated I-1 is shown. The time of TPS is indicated by the arrow. Thiophosphorylated I-1 (Thio-P I-1; 10 \u0026#x3BC;m; n = 9) or inactive, nonphosphorylatable I-1 (T35A I-1; 10 \u0026#x3BC;m; n = 8) was applied in the intracellular electrode. A slowly developing LTP was induced by TPS only when thiophosphorylated I-1 was present, with the two groups differing significantly over the last three time points of the experiment (ANOVA, p \u0026lt; 0.05).Inset, Sample intracellular and fieldtraces (top and bottom panels, respectively) from a T35A I-1 experiment (left) and a Thio-P I-1 experiment (right) are shown. Presentation details are as described in Figure 1. No field LTP was obtained in any of the slices in this experiment. Calibration: 10 mV intracellular, 250 \u0026#x3BC;V extracellular; 5 msec. C2 , Summary data of intracellular and field data at 30 min after TPS are shown. The intracellular data were derived from the experiment shown in C1. CON, Control.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-990087893\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;The role of protein phosphatase-1 in TPS-induced LTP. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;, Protein phosphatase activity in CA1 is inhibited by activation of the cAMP pathway. In slices exposed to 1 mm 8-Br-cAMP for 30 min, total phosphatase activity was significantly lower than that in untreated controls (\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.05). Similar results were obtained in two independent experiments. The selectivity of the assay for PP1 is shown by the ability of 100 nm thiophosphorylated inhibitor-1 (I-1-P) to block \u0026gt;85% of total phosphatase activity, indicated by the \u0026lt;em\u0026gt;black bar\u0026lt;\/em\u0026gt; and \u0026lt;em\u0026gt;dashed line\u0026lt;\/em\u0026gt;. \u0026lt;em\u0026gt;B\u0026lt;\/em\u0026gt;, Endogenous protein phosphatase inhibitor-1 is phosphorylated by stimulation of the cAMP pathway. Tissue homogenates were probed with a monoclonal antibody recognizing either the phosphorylated form of inhibitor-1 selectively (\u0026lt;em\u0026gt;top gel\u0026lt;\/em\u0026gt;) or both the phosphorylated and nonphosphorylated inhibitor-1 (\u0026lt;em\u0026gt;bottom gel\u0026lt;\/em\u0026gt;). Isoproterenol (10 \u0026#x3BC;m) and 8-Br-cAMP (500 \u0026#x3BC;m) increased the levels of Thr\u0026lt;sup\u0026gt;35\u0026lt;\/sup\u0026gt;-phosphorylated I-1 4.04 (\u0026#xB1; 2.28)-fold and 2.75 (\u0026#xB1; 0.62)-fold, respectively, relative to unstimulated tissue and normalized for total I-1 levels. Both isoproterenol and 8-Br-cAMP increased the level of thiophosphorylated inhibitor-1 (\u0026lt;em\u0026gt;top gel\u0026lt;\/em\u0026gt;) without significantly changing the total amount of inhibitor-1. Similar results were obtained in two other experiments.\u0026lt;em\u0026gt;C\u0026lt;\/em\u0026gt;, Postsynaptic inhibition of PP1 mimics cAMP pathway activation in TPS-LTP. \u0026lt;em\u0026gt;C\u0026lt;\/em\u0026gt;\u0026lt;sub\u0026gt;\u0026lt;em\u0026gt;1\u0026lt;\/em\u0026gt;\u0026lt;\/sub\u0026gt;, The time course of LTP induced by TPS paired with thiophosphorylated I-1 is shown. The time of TPS is indicated by the \u0026lt;em\u0026gt;arrow\u0026lt;\/em\u0026gt;. Thiophosphorylated I-1 (\u0026lt;em\u0026gt;Thio-P I-1\u0026lt;\/em\u0026gt;; 10 \u0026#x3BC;m; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 9) or inactive, nonphosphorylatable I-1 (\u0026lt;em\u0026gt;T35A I-1\u0026lt;\/em\u0026gt;; 10 \u0026#x3BC;m; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 8) was applied in the intracellular electrode. A slowly developing LTP was induced by TPS only when thiophosphorylated I-1 was present, with the two groups differing significantly over the last three time points of the experiment (ANOVA, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.05).\u0026lt;em\u0026gt;Inset\u0026lt;\/em\u0026gt;, Sample intracellular and field\u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt; (\u0026lt;em\u0026gt;top\u0026lt;\/em\u0026gt; and \u0026lt;em\u0026gt;bottom panels\u0026lt;\/em\u0026gt;, respectively) from a \u0026lt;em\u0026gt;T35A I-1\u0026lt;\/em\u0026gt; experiment (\u0026lt;em\u0026gt;left\u0026lt;\/em\u0026gt;) and a \u0026lt;em\u0026gt;Thio-P I-1\u0026lt;\/em\u0026gt; experiment (\u0026lt;em\u0026gt;right\u0026lt;\/em\u0026gt;) are shown. Presentation details are as described in Figure 1. No field LTP was obtained in any of the slices in this experiment. Calibration: 10 mV intracellular, 250 \u0026#x3BC;V extracellular; 5 msec. \u0026lt;em\u0026gt;C\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt; \u0026lt;\/em\u0026gt;, Summary data of intracellular and field data at 30 min after TPS are shown. The intracellular data were derived from the experiment shown in C\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;. \u0026lt;em\u0026gt;CON\u0026lt;\/em\u0026gt;, Control.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 3.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F3.medium.gif\u0022 width=\u0022172\u0022 height=\u0022440\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 3.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F3.medium.gif\u0022 width=\u0022172\u0022 height=\u0022440\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/421050\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 3.\u003C\/span\u003E \u003Cp id=\u0022p-20\u0022\u003EThe role of protein phosphatase-1 in TPS-induced LTP. \u003Cem\u003EA\u003C\/em\u003E, Protein phosphatase activity in CA1 is inhibited by activation of the cAMP pathway. In slices exposed to 1 m\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E 8-Br-cAMP for 30 min, total phosphatase activity was significantly lower than that in untreated controls (\u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.05). Similar results were obtained in two independent experiments. The selectivity of the assay for PP1 is shown by the ability of 100 n\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E thiophosphorylated inhibitor-1 (I-1-P) to block \u0026gt;85% of total phosphatase activity, indicated by the \u003Cem\u003Eblack bar\u003C\/em\u003E and \u003Cem\u003Edashed line\u003C\/em\u003E. \u003Cem\u003EB\u003C\/em\u003E, Endogenous protein phosphatase inhibitor-1 is phosphorylated by stimulation of the cAMP pathway. Tissue homogenates were probed with a monoclonal antibody recognizing either the phosphorylated form of inhibitor-1 selectively (\u003Cem\u003Etop gel\u003C\/em\u003E) or both the phosphorylated and nonphosphorylated inhibitor-1 (\u003Cem\u003Ebottom gel\u003C\/em\u003E). Isoproterenol (10 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) and 8-Br-cAMP (500 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) increased the levels of Thr\u003Csup\u003E35\u003C\/sup\u003E-phosphorylated I-1 4.04 (\u00b1 2.28)-fold and 2.75 (\u00b1 0.62)-fold, respectively, relative to unstimulated tissue and normalized for total I-1 levels. Both isoproterenol and 8-Br-cAMP increased the level of thiophosphorylated inhibitor-1 (\u003Cem\u003Etop gel\u003C\/em\u003E) without significantly changing the total amount of inhibitor-1. Similar results were obtained in two other experiments.\u003Cem\u003EC\u003C\/em\u003E, Postsynaptic inhibition of PP1 mimics cAMP pathway activation in TPS-LTP. \u003Cem\u003EC\u003C\/em\u003E\u003Csub\u003E\u003Cem\u003E1\u003C\/em\u003E\u003C\/sub\u003E, The time course of LTP induced by TPS paired with thiophosphorylated I-1 is shown. The time of TPS is indicated by the \u003Cem\u003Earrow\u003C\/em\u003E. Thiophosphorylated I-1 (\u003Cem\u003EThio-P I-1\u003C\/em\u003E; 10 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E; \u003Cem\u003En\u003C\/em\u003E = 9) or inactive, nonphosphorylatable I-1 (\u003Cem\u003ET35A I-1\u003C\/em\u003E; 10 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E; \u003Cem\u003En\u003C\/em\u003E = 8) was applied in the intracellular electrode. A slowly developing LTP was induced by TPS only when thiophosphorylated I-1 was present, with the two groups differing significantly over the last three time points of the experiment (ANOVA, \u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.05).\u003Cem\u003EInset\u003C\/em\u003E, Sample intracellular and field\u003Cem\u003Etraces\u003C\/em\u003E (\u003Cem\u003Etop\u003C\/em\u003E and \u003Cem\u003Ebottom panels\u003C\/em\u003E, respectively) from a \u003Cem\u003ET35A I-1\u003C\/em\u003E experiment (\u003Cem\u003Eleft\u003C\/em\u003E) and a \u003Cem\u003EThio-P I-1\u003C\/em\u003E experiment (\u003Cem\u003Eright\u003C\/em\u003E) are shown. Presentation details are as described in Figure \u003Cspan id=\u0022xref-fig-1-5\u0022 class=\u0022xref-fig\u0022\u003E1\u003C\/span\u003E. No field LTP was obtained in any of the slices in this experiment. Calibration: 10 mV intracellular, 250 \u03bcV extracellular; 5 msec. \u003Cem\u003EC\u003Csub\u003E2\u003C\/sub\u003E\n\u003C\/em\u003E, Summary data of intracellular and field data at 30 min after TPS are shown. The intracellular data were derived from the experiment shown in C\u003Csub\u003E1\u003C\/sub\u003E. \u003Cem\u003ECON\u003C\/em\u003E, Control.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion \u0022 id=\u0022F4\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F4.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022CaMKII integrates TPS and cAMP pathway stimulation. A, Postsynaptic CaMKII activity is required for TPS-LTP. A1, Time course graph of intracellular EPSPs is shown. The horizontal barindicates isoproterenol application, and the arrow near the x-axis shows the time of TPS. The intracellular electrode contained either inactive control peptide (5 mm; filled symbols;n = 5) or the CaMKII inhibitor autocamtide-3 (AC3; 5 mm; open symbols; n = 5). Normal LTP was obtained in the control cells, but LTP was absent in cells injected withAC3. The groups differed significantly over the last three time points (ANOVA, p \u0026lt; 0.01).Inset, Representative intracellular and field EPSPs from a control peptide experiment (left) and from anAC3 experiment (right) are shown. Presentation details are as described in Figure 1. Calibration: 10 mV intracellular, 250 \u0026#x3BC;V extracellular; 10 msec.A2 , Summary graph of data recorded at 30 min after TPS is shown. The filled bars represent changes in intracellular synaptic strength, and the hatched bars represent field data. Con Pep, Peptide control for AC3. The only group to exhibit intracellular LTP was the combined TPS plus Con Pepgroup, which was significantly different from both other groups (Newman\u0026#x2013;Keuls test, p values \u0026lt; 0.05).B, TPS paired with 8-Br-cAMP (500 \u0026#x3BC;m) increases Ca2+-independent CaMKII activity. Similar results were obtained in three independent experiments, one of which is shown here. The slices that were exposed to the combination treatment showed significantly greater CaMKII activity in the absence of Ca2+ than did all other groups (Newman\u0026#x2013;Keuls test, *p \u0026lt; 0.05), which did not differ among themselves. No group differences in total CaMKII activity were observed (ANOVA,p \u0026gt; 0.20; mean activity = 3.29 \u0026#xB1; 0.39 pmol\u0026#xB7;\u0026#x3BC;g\u0026#x2212;1\u0026#xB7;min\u0026#x2212;1 pooled across groups). C, The blockade of LTP by a CaMKII inhibitor is resistant to PP1 suppression. Summary of results from experiments in which LTP was induced using TPS, with data taken from the final three time points (26\u0026#x2013;30 min after TPS), is shown. Substances were applied in the intracellular recording electrode. Autocamtide-3 (2.5 mm) was combined either with nonphosphorylatable T35A I-1 (T35A;filled bar; n = 6) or with thiophosphorylated I-1 (ThioP; hatched bar; n = 6). In other cells, thiophosphorylated I-1 was presented with the control peptide for autocamtide-3 (2.5 mm; open bar;n = 6). The asterisk indicates a significant increase in EPSP slope above baseline (ANOVA,p \u0026lt; 0.05).\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-990087893\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;CaMKII integrates TPS and cAMP pathway stimulation. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;, Postsynaptic CaMKII activity is required for TPS-LTP. \u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;\u0026lt;sub\u0026gt;\u0026lt;em\u0026gt;1\u0026lt;\/em\u0026gt;\u0026lt;\/sub\u0026gt;, Time course graph of intracellular EPSPs is shown. The \u0026lt;em\u0026gt;horizontal bar\u0026lt;\/em\u0026gt;indicates isoproterenol application, and the \u0026lt;em\u0026gt;arrow\u0026lt;\/em\u0026gt; near the \u0026lt;em\u0026gt;x\u0026lt;\/em\u0026gt;-axis shows the time of TPS. The intracellular electrode contained either inactive control peptide (5 mm; \u0026lt;em\u0026gt;filled symbols\u0026lt;\/em\u0026gt;;\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5) or the CaMKII inhibitor autocamtide-3 (\u0026lt;em\u0026gt;AC3\u0026lt;\/em\u0026gt;; 5 mm; \u0026lt;em\u0026gt;open symbols\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 5). Normal LTP was obtained in the control cells, but LTP was absent in cells injected with\u0026lt;em\u0026gt;AC3\u0026lt;\/em\u0026gt;. The groups differed significantly over the last three time points (ANOVA, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.01).\u0026lt;em\u0026gt;Inset\u0026lt;\/em\u0026gt;, Representative intracellular and field EPSPs from a control peptide experiment (\u0026lt;em\u0026gt;left\u0026lt;\/em\u0026gt;) and from an\u0026lt;em\u0026gt;AC3\u0026lt;\/em\u0026gt; experiment (\u0026lt;em\u0026gt;right\u0026lt;\/em\u0026gt;) are shown. Presentation details are as described in Figure 1. Calibration: 10 mV intracellular, 250 \u0026#x3BC;V extracellular; 10 msec.\u0026lt;em\u0026gt;A\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt; \u0026lt;\/em\u0026gt;, Summary graph of data recorded at 30 min after TPS is shown. The \u0026lt;em\u0026gt;filled bars\u0026lt;\/em\u0026gt; represent changes in intracellular synaptic strength, and the \u0026lt;em\u0026gt;hatched bars\u0026lt;\/em\u0026gt; represent field data. \u0026lt;em\u0026gt;Con Pep\u0026lt;\/em\u0026gt;, Peptide control for \u0026lt;em\u0026gt;AC3\u0026lt;\/em\u0026gt;. The only group to exhibit intracellular LTP was the combined TPS plus \u0026lt;em\u0026gt;Con Pep\u0026lt;\/em\u0026gt;group, which was significantly different from both other groups (Newman\u0026#x2013;Keuls test, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; values \u0026lt; 0.05).\u0026lt;em\u0026gt;B\u0026lt;\/em\u0026gt;, TPS paired with 8-Br-cAMP (500 \u0026#x3BC;m) increases Ca\u0026lt;sup\u0026gt;2+\u0026lt;\/sup\u0026gt;-independent CaMKII activity. Similar results were obtained in three independent experiments, one of which is shown here. The slices that were exposed to the combination treatment showed significantly greater CaMKII activity in the absence of Ca\u0026lt;sup\u0026gt;2+\u0026lt;\/sup\u0026gt; than did all other groups (Newman\u0026#x2013;Keuls test, *\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.05), which did not differ among themselves. No group differences in total CaMKII activity were observed (ANOVA,\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026gt; 0.20; mean activity = 3.29 \u0026#xB1; 0.39 pmol\u0026#xB7;\u0026#x3BC;g\u0026lt;sup\u0026gt;\u0026#x2212;1\u0026lt;\/sup\u0026gt;\u0026#xB7;min\u0026lt;sup\u0026gt;\u0026#x2212;1\u0026lt;\/sup\u0026gt; pooled across groups). \u0026lt;em\u0026gt;C\u0026lt;\/em\u0026gt;, The blockade of LTP by a CaMKII inhibitor is resistant to PP1 suppression. Summary of results from experiments in which LTP was induced using TPS, with data taken from the final three time points (26\u0026#x2013;30 min after TPS), is shown. Substances were applied in the intracellular recording electrode. Autocamtide-3 (2.5 mm) was combined either with nonphosphorylatable \u0026lt;em\u0026gt;T35A I-1\u0026lt;\/em\u0026gt; (\u0026lt;em\u0026gt;T35A\u0026lt;\/em\u0026gt;;\u0026lt;em\u0026gt;filled bar\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 6) or with thiophosphorylated I-1 (\u0026lt;em\u0026gt;ThioP\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;hatched bar\u0026lt;\/em\u0026gt;; \u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 6). In other cells, thiophosphorylated I-1 was presented with the control peptide for autocamtide-3 (2.5 mm; \u0026lt;em\u0026gt;open bar\u0026lt;\/em\u0026gt;;\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 6). The \u0026lt;em\u0026gt;asterisk\u0026lt;\/em\u0026gt; indicates a significant increase in EPSP slope above baseline (ANOVA,\u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.05).\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 4.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F4.medium.gif\u0022 width=\u0022440\u0022 height=\u0022373\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 4.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F4.medium.gif\u0022 width=\u0022440\u0022 height=\u0022373\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F4.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 4.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F4.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/421052\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 4.\u003C\/span\u003E \u003Cp id=\u0022p-25\u0022\u003ECaMKII integrates TPS and cAMP pathway stimulation. \u003Cem\u003EA\u003C\/em\u003E, Postsynaptic CaMKII activity is required for TPS-LTP. \u003Cem\u003EA\u003C\/em\u003E\u003Csub\u003E\u003Cem\u003E1\u003C\/em\u003E\u003C\/sub\u003E, Time course graph of intracellular EPSPs is shown. The \u003Cem\u003Ehorizontal bar\u003C\/em\u003Eindicates isoproterenol application, and the \u003Cem\u003Earrow\u003C\/em\u003E near the \u003Cem\u003Ex\u003C\/em\u003E-axis shows the time of TPS. The intracellular electrode contained either inactive control peptide (5 m\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E; \u003Cem\u003Efilled symbols\u003C\/em\u003E;\u003Cem\u003En\u003C\/em\u003E = 5) or the CaMKII inhibitor autocamtide-3 (\u003Cem\u003EAC3\u003C\/em\u003E; 5 m\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E; \u003Cem\u003Eopen symbols\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 5). Normal LTP was obtained in the control cells, but LTP was absent in cells injected with\u003Cem\u003EAC3\u003C\/em\u003E. The groups differed significantly over the last three time points (ANOVA, \u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.01).\u003Cem\u003EInset\u003C\/em\u003E, Representative intracellular and field EPSPs from a control peptide experiment (\u003Cem\u003Eleft\u003C\/em\u003E) and from an\u003Cem\u003EAC3\u003C\/em\u003E experiment (\u003Cem\u003Eright\u003C\/em\u003E) are shown. Presentation details are as described in Figure \u003Cspan id=\u0022xref-fig-1-6\u0022 class=\u0022xref-fig\u0022\u003E1\u003C\/span\u003E. Calibration: 10 mV intracellular, 250 \u03bcV extracellular; 10 msec.\u003Cem\u003EA\u003Csub\u003E2\u003C\/sub\u003E\n\u003C\/em\u003E, Summary graph of data recorded at 30 min after TPS is shown. The \u003Cem\u003Efilled bars\u003C\/em\u003E represent changes in intracellular synaptic strength, and the \u003Cem\u003Ehatched bars\u003C\/em\u003E represent field data. \u003Cem\u003ECon Pep\u003C\/em\u003E, Peptide control for \u003Cem\u003EAC3\u003C\/em\u003E. The only group to exhibit intracellular LTP was the combined TPS plus \u003Cem\u003ECon Pep\u003C\/em\u003Egroup, which was significantly different from both other groups (Newman\u2013Keuls test, \u003Cem\u003Ep\u003C\/em\u003E values \u0026lt; 0.05).\u003Cem\u003EB\u003C\/em\u003E, TPS paired with 8-Br-cAMP (500 \u03bc\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) increases Ca\u003Csup\u003E2+\u003C\/sup\u003E-independent CaMKII activity. Similar results were obtained in three independent experiments, one of which is shown here. The slices that were exposed to the combination treatment showed significantly greater CaMKII activity in the absence of Ca\u003Csup\u003E2+\u003C\/sup\u003E than did all other groups (Newman\u2013Keuls test, *\u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.05), which did not differ among themselves. No group differences in total CaMKII activity were observed (ANOVA,\u003Cem\u003Ep\u003C\/em\u003E \u0026gt; 0.20; mean activity = 3.29 \u00b1 0.39 pmol\u00b7\u03bcg\u003Csup\u003E\u22121\u003C\/sup\u003E\u00b7min\u003Csup\u003E\u22121\u003C\/sup\u003E pooled across groups). \u003Cem\u003EC\u003C\/em\u003E, The blockade of LTP by a CaMKII inhibitor is resistant to PP1 suppression. Summary of results from experiments in which LTP was induced using TPS, with data taken from the final three time points (26\u201330 min after TPS), is shown. Substances were applied in the intracellular recording electrode. Autocamtide-3 (2.5 m\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E) was combined either with nonphosphorylatable \u003Cem\u003ET35A I-1\u003C\/em\u003E (\u003Cem\u003ET35A\u003C\/em\u003E;\u003Cem\u003Efilled bar\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 6) or with thiophosphorylated I-1 (\u003Cem\u003EThioP\u003C\/em\u003E; \u003Cem\u003Ehatched bar\u003C\/em\u003E; \u003Cem\u003En\u003C\/em\u003E = 6). In other cells, thiophosphorylated I-1 was presented with the control peptide for autocamtide-3 (2.5 m\u003Cspan class=\u0022sc\u0022\u003Em\u003C\/span\u003E; \u003Cem\u003Eopen bar\u003C\/em\u003E;\u003Cem\u003En\u003C\/em\u003E = 6). The \u003Cem\u003Easterisk\u003C\/em\u003E indicates a significant increase in EPSP slope above baseline (ANOVA,\u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.05).\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli class=\u0022last\u0022\u003E\u003Cdiv class=\u0022element-fig-data clearfix figure-caption\u0022\u003E\u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022fig-expansion \u0022 id=\u0022F5\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F5.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The direct inhibition of postsynaptic PP1 enables TPS-induced LTP without an increase in postsynaptic spiking.A, Postsynaptic activity during TPS was not increased by thiophosphorylated I-1.A1, Samples of postsynaptic potentials recorded just before TPS (PRE) and at every 30th stimulus during TPS are shown. Double spikes were evoked during TPS in both groups. Of all TPS samples recorded (n = 85), only one stimulus produced three spikes, with all of the others yielding one or two. Calibration: 10 mV; 10 msec.A2 , Summary of the number of spikes produced by stimuli during TPS is shown. There were no statistically significant differences between cells recorded with thiophosphorylated I-1 and those recorded with T35A I-1. A patterning effect was obtained, with the number of spikes at trace90 significantly higher than those at traces 30 and 150 (Newman\u0026#x2013;Keuls, p \u0026lt; 0.01 and 0.05, respectively). B, TPS induces LTP when paired with intracellular application of thiophosphorylated I-1. Only cells impaled with Thio-P I-1 (n = 10) showed LTP after TPS. The rapid induction of LTP compared with that shown in Figure 3 is probably caused by the stronger stimulation used during TPS (see Materials and Methods). No lasting effect on synaptic efficiency was seen when TPS was delivered to cells impaled with electrodes containing inactive T35A I-1 (n = 7). The inset shows sample EPSPs obtained during the baseline period and at 60 min after TPS.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-990087893\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;The direct inhibition of postsynaptic PP1 enables TPS-induced LTP without an increase in postsynaptic spiking.\u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;, Postsynaptic activity during TPS was not increased by thiophosphorylated I-1.\u0026lt;em\u0026gt;A\u0026lt;\/em\u0026gt;\u0026lt;sub\u0026gt;\u0026lt;em\u0026gt;1\u0026lt;\/em\u0026gt;\u0026lt;\/sub\u0026gt;, Samples of postsynaptic potentials recorded just before TPS (\u0026lt;em\u0026gt;PRE\u0026lt;\/em\u0026gt;) and at every 30th stimulus during TPS are shown. Double spikes were evoked during TPS in both groups. Of all TPS samples recorded (\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 85), only one stimulus produced three spikes, with all of the others yielding one or two. Calibration: 10 mV; 10 msec.\u0026lt;em\u0026gt;A\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt; \u0026lt;\/em\u0026gt;, Summary of the number of spikes produced by stimuli during TPS is shown. There were no statistically significant differences between cells recorded with thiophosphorylated I-1 and those recorded with \u0026lt;em\u0026gt;T35A I-1\u0026lt;\/em\u0026gt;. A patterning effect was obtained, with the number of spikes at \u0026lt;em\u0026gt;trace\u0026lt;\/em\u0026gt;90 significantly higher than those at \u0026lt;em\u0026gt;traces\u0026lt;\/em\u0026gt; 30 and 150 (Newman\u0026#x2013;Keuls, \u0026lt;em\u0026gt;p\u0026lt;\/em\u0026gt; \u0026lt; 0.01 and 0.05, respectively). \u0026lt;em\u0026gt;B\u0026lt;\/em\u0026gt;, TPS induces LTP when paired with intracellular application of thiophosphorylated I-1. Only cells impaled with \u0026lt;em\u0026gt;Thio-P I-1\u0026lt;\/em\u0026gt; (\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 10) showed LTP after TPS. The rapid induction of LTP compared with that shown in Figure 3 is probably caused by the stronger stimulation used during TPS (see Materials and Methods). No lasting effect on synaptic efficiency was seen when TPS was delivered to cells impaled with electrodes containing inactive \u0026lt;em\u0026gt;T35A I-1\u0026lt;\/em\u0026gt; (\u0026lt;em\u0026gt;n\u0026lt;\/em\u0026gt; = 7). The \u0026lt;em\u0026gt;inset \u0026lt;\/em\u0026gt;shows sample EPSPs obtained during the baseline period and at 60 min after TPS.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 5.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F5.medium.gif\u0022 width=\u0022203\u0022 height=\u0022440\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 5.\u0022 src=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F5.medium.gif\u0022 width=\u0022203\u0022 height=\u0022440\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F5.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 5.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022http:\/\/www.jneurosci.org\/content\/jneuro\/20\/21\/7880\/F5.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/421054\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 5.\u003C\/span\u003E \u003Cp id=\u0022p-30\u0022\u003EThe direct inhibition of postsynaptic PP1 enables TPS-induced LTP without an increase in postsynaptic spiking.\u003Cem\u003EA\u003C\/em\u003E, Postsynaptic activity during TPS was not increased by thiophosphorylated I-1.\u003Cem\u003EA\u003C\/em\u003E\u003Csub\u003E\u003Cem\u003E1\u003C\/em\u003E\u003C\/sub\u003E, Samples of postsynaptic potentials recorded just before TPS (\u003Cem\u003EPRE\u003C\/em\u003E) and at every 30th stimulus during TPS are shown. Double spikes were evoked during TPS in both groups. Of all TPS samples recorded (\u003Cem\u003En\u003C\/em\u003E = 85), only one stimulus produced three spikes, with all of the others yielding one or two. Calibration: 10 mV; 10 msec.\u003Cem\u003EA\u003Csub\u003E2\u003C\/sub\u003E\n\u003C\/em\u003E, Summary of the number of spikes produced by stimuli during TPS is shown. There were no statistically significant differences between cells recorded with thiophosphorylated I-1 and those recorded with \u003Cem\u003ET35A I-1\u003C\/em\u003E. A patterning effect was obtained, with the number of spikes at \u003Cem\u003Etrace\u003C\/em\u003E90 significantly higher than those at \u003Cem\u003Etraces\u003C\/em\u003E 30 and 150 (Newman\u2013Keuls, \u003Cem\u003Ep\u003C\/em\u003E \u0026lt; 0.01 and 0.05, respectively). \u003Cem\u003EB\u003C\/em\u003E, TPS induces LTP when paired with intracellular application of thiophosphorylated I-1. Only cells impaled with \u003Cem\u003EThio-P I-1\u003C\/em\u003E (\u003Cem\u003En\u003C\/em\u003E = 10) showed LTP after TPS. The rapid induction of LTP compared with that shown in Figure \u003Cspan id=\u0022xref-fig-3-4\u0022 class=\u0022xref-fig\u0022\u003E3\u003C\/span\u003E is probably caused by the stronger stimulation used during TPS (see Materials and Methods). No lasting effect on synaptic efficiency was seen when TPS was delivered to cells impaled with electrodes containing inactive \u003Cem\u003ET35A I-1\u003C\/em\u003E (\u003Cem\u003En\u003C\/em\u003E = 7). The \u003Cem\u003Einset \u003C\/em\u003Eshows sample EPSPs obtained during the baseline period and at 60 min after TPS.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003Cdiv class=\u0022panel-separator\u0022\u003E\u003C\/div\u003E\u003Cdiv class=\u0022panel-pane pane-earthchem\u0022 \u003E\n \n \n \n \u003Cdiv class=\u0022pane-content\u0022\u003E\n \u003Ca href=\u0022http:\/\/ecp.iedadata.org\/doidata\/10.1523\/JNEUROSCI.20-21-07880.2000\u0022 class=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg src=\u0022http:\/\/ecp.iedadata.org\/doibanner\/10.1523\/JNEUROSCI.20-21-07880.2000\u0022 alt=\u0022\u0022 \/\u003E\u003C\/a\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 defer=\u0022defer\u0022 src=\u0022http:\/\/www.jneurosci.org\/sites\/all\/libraries\/lazysizes\/lazysizes.min.js?pl7981\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/www.jneurosci.org\/sites\/default\/files\/js\/js_jhC2x8JTBVea3SQI9MHvrE-xvEYbkkl15LxsCvMXt6U.js\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}